Monoclonal Anti-P-glycoprotein Antibody-dependent Killing of Multidrug-resistant Tumor Cells by Human Mononuclear Cells |
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| Authors: | Yuji Heike Hirofumi Hamada Noriaki Inamura Saburo Sone Takeshi Ogura Takashi Tsuruo |
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| Affiliation: | Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1, Kami-Ikebukuro, Toshima-ku, Tokyo 170;The Third Department of Internal Medicine, The University of Tokushima, School of Medicine, Kuramoto-cho, Tokushima 770;Institute of Applied Microbiology, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113 |
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| Abstract: | Mouse monoclonal antibodies (MRK16 and MRK17) against human multidrug-resistant cancer cell lines were tested for antibody-dependent cytotoxicity mediated by human blood mononuclear cells, using a 4-h 51Cr release assay. MRK16 (IgG28 isotype) was shown to be more effective than MRK17 (IgG1 isotype). Moreover, when four pairs of drug-resistant and their parent sensitive human cancer cells were tested for antibody-dependent cell-mediated cytolysis (ADCC) using MRK16, only the drug-resistant cell lines were susceptible to ADCC reaction. When highly purified lymphocytes (>99%) and monocytes (>97%) were isolated from blood mononuclear cells by centrifugal elutriation and adherence, MRK16 promoted both lymphocyte- and monocyte-mediated tumor cell killing, whereas MRK17 induced only a lymphocyte-mediated ADCC reaction. These results suggest that MRK16 of IgG28 subtype may be a useful therapeutic agent in eradication of drug-resistant cancer cells expressing P-glycoprotein through ADCC reaction. |
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| Keywords: | Multidrug resistance P-glycoprotein Monoclonal antibody Human mononuclear cells |
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